The commonest side-effects of efavirenz occur in the brain. Trials have shown that between 14 and 50% of people who take efavirenz develop side-effects in the first few months of treatment including drowsiness or insomnia, dizziness, vivid dreams and nightmares, confusion, abnormal thinking, impaired concentration, loss of memory, agitation, feeling ‘out-of-sorts’ or ‘stoned’, hallucinations, delusions, euphoria and depression^[1]. Some of these side-effects are attributed to the detrimental impact efavirenz has on sleep.

The existence of the psychiatric side-effects of efavirenz, including depression, suicidal ideation, aggression, paranoia and mania is controversial. Some studies have found no links between these effects and efavirenz use^[2]. If they are real, however, it is certain that they are rare, although they may be more common in people with a history of psychiatric disorders^[3]. Only 1% of patients in trials discontinued efavirenz due to psychiatric side-effects.

Side-effects are most likely to occur in the first two to four weeks of treatment, after which they tend to diminish markedly^[4]. However, there is some evidence that symptoms like mild anxiety and bad dreams may persist in up to half of patients for over six months, or even while treatment continues^[5][6][7]. Despite their frequency, most people experience only mild to moderate symptoms, and trials indicate that only 3% of people cease efavirenz due to side-effects.

The manufacturer currently recommends that efavirenz be taken before going to bed, since the feelings of dizziness and anxiety are likely to be most intense in the hours leading up to the peak in drug levels, around four hours after dosing. However, up to half of patients prefer to take efavirenz in the morning, to avoid the bad dreams, disturbed sleep and morning drowsiness that the drug can cause^[8].

Some people clear efavirenz more slowly than others due to a particular genetic variation. This genetic variation is common among people with a black African heritage and it may increase the risk of side-effects^[9][10][11]. For example, one women from Ghana developed psychosis after a week’s treatment with efavirenz, with paranoid hallucinations and anxiety, resulting in her stabbing a nurse^[12]. Testing is not currently available to find out who has this particular genetic make-up. However, therapeutic drug monitoring may be used to identify people who are being exposed to high concentrations of efavirenz. For more information, see Metabolising enzymes.

Rash is also common in people taking efavirenz, affecting around a quarter of people in trials. It can usually be controlled using antihistamines, and tends to resolve within a month of starting efavirenz-based therapy.

Elevated liver enzymes were reported in 2% of the patients taking efavirenz in study 006^[13]. These are more common in patients co-infected with hepatitis B or C.

Less common side-effects of efavirenz include headache, alcohol intolerance, fever, aches, pains and fatigue, fluid retention in the hands and feet, dry mouth, elevated lipid levels, pancreatitis, skin problems, asthma and changes to vision and taste. Interestingly, reports of lipid elevations have included rises in high-density lipoprotein (HDL) or ‘good’ cholesterol, particularly in people with a genetic polymorphism in the multidrug resistance gene 1^[14][15]. However, levels of total cholesterol also increase, resulting in a small net increase in the ratio of total to HDL cholesterol^[16]. This study also found that efavirenz causes elevations in triglyceride levels.

Gynaecomastia (enlargement of the breasts) has been observed in a small number of patients taking efavirenz^[17][18][19]. A hypersensitivity reaction to efavirenz has also been reported in two individuals. Symptoms included rash, fever, abdominal pain, diarrhoea, dry cough and jaundice^[20]. In the second case, the hypersensitivity reaction also involved the lungs^[21]. One case of a urinary stone caused by efavirenz has also been reported^[22]. A case of anaemia due to the breakdown of red blood cells has also been attributed to efavirenz treatment^[23].